The objective of this study is the development of an animal model of protease inhibitor deficiency which can be used to evaluate the role of serum and tissue protease inhibitors in human pulmonary emphysema. This objective is being accomplished by the following studies: 1) Analysis of the effects of certain antimetabolites on the serum protease inhibitor and in producing hepatic cytoplasmic PAS positive inclusion. D-galactosamine (D-gal) is particularly good agent; 6-azauridine and 2 deoxyglucose are also being studied. 2) Test the effect of depressing serum protease inhibitors with a standard quantitatively evaluated model of elastase emphysema produced by aerosol on intratracheal inoculation. 3) Evaluate the effect of acetylalanyl-alanyl-prolyl-alanyl-chloromethylketone (APPACMK) on pancreatic elastase in vitro and in vivo. The in vivo evaluation will be based on the inhibitory effect of AAPACMK or a test model of elastase induced emphysema. 4) To collect, concentrate and quantitate the elastases from neutrophils and macrophages collected from the peritoneal cavity. To attempt to increase the amount of elastase contained within the leucocytes by the treatment with particulate or soluble elastin, by administration of Freuds adjuvant, endotoxin or pyrogens. To test the effect of AAPACMK or the activity of leucocyte elastases and collagenases. 5) To collect and purify hepatic protease inhibitors (PI) from isolated liver perfusion in experimental animals to characterize these PI chemically, biochemically for molecular weight, immunologic identity with serum PI in normal and D-Gal treated animals. BIBLIOGRAPHIC REFERENCES: Liotta, L.A., Saidel, G.M., and Kleinerman, J.: A Stochastic Model of Metastasis Formation. Biometrics. 32:535-550, 1976. Saidel, G.M., Liotta, L.A., and Kleinerman, J.: System Dynamics of a Metastatic Process from an Implanted Tumor. J. Theoretical Biology. 56:417, 1976.